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Cooperative Chikungunya Virus Membrane Fusion and Its Substoichiometric Inhibition by CHK-152 Antibody

Journal Article


Abstract


  • Chikungunya virus (CHIKV) presents a major burden on healthcare systems worldwide, but specific treatment remains unavailable. Attachment and fusion of CHIKV to the host cell membrane is mediated by the E1/E2 protein spikes. We used an in vitro single-particle fusion assay to study the effect of the potent, neutralizing antibody CHK-152 on CHIKV binding and fusion. We find that CHK-152 shields the virions, inhibiting interaction with the target membrane and inhibiting fusion. The analysis of the ratio of bound antibodies to epitopes implied that CHIKV fusion is a highly cooperative process. Further, dissociation of the antibody at lower pH results in a finely balanced kinetic competition between inhibition and fusion, suggesting a window of opportunity for the spike proteins to act and mediate fusion, even in the presence of the antibody.

Publication Date


  • 2022

Citation


  • Blijleven, J. S., Bouma, E. M., van Duijl-Richter, M. K. S., Smit, J. M., & van Oijen, A. M. (2022). Cooperative Chikungunya Virus Membrane Fusion and Its Substoichiometric Inhibition by CHK-152 Antibody. Viruses, 14(2). doi:10.3390/v14020270

Scopus Eid


  • 2-s2.0-85123527727

Web Of Science Accession Number


Volume


  • 14

Issue


  • 2

Abstract


  • Chikungunya virus (CHIKV) presents a major burden on healthcare systems worldwide, but specific treatment remains unavailable. Attachment and fusion of CHIKV to the host cell membrane is mediated by the E1/E2 protein spikes. We used an in vitro single-particle fusion assay to study the effect of the potent, neutralizing antibody CHK-152 on CHIKV binding and fusion. We find that CHK-152 shields the virions, inhibiting interaction with the target membrane and inhibiting fusion. The analysis of the ratio of bound antibodies to epitopes implied that CHIKV fusion is a highly cooperative process. Further, dissociation of the antibody at lower pH results in a finely balanced kinetic competition between inhibition and fusion, suggesting a window of opportunity for the spike proteins to act and mediate fusion, even in the presence of the antibody.

Publication Date


  • 2022

Citation


  • Blijleven, J. S., Bouma, E. M., van Duijl-Richter, M. K. S., Smit, J. M., & van Oijen, A. M. (2022). Cooperative Chikungunya Virus Membrane Fusion and Its Substoichiometric Inhibition by CHK-152 Antibody. Viruses, 14(2). doi:10.3390/v14020270

Scopus Eid


  • 2-s2.0-85123527727

Web Of Science Accession Number


Volume


  • 14

Issue


  • 2